03 March 2014

Cancer - A Metabolic Disease

Cancer seems to be unstoppable according to this article: Worldwide cancer cases expected to soar by 70% over next 20 years.
"The incidence of cancer globally has increased in just four years from 12.7m in 2008 to 14.1m new cases in 2012, when there were 8.2m deaths. Over the next 20 years, it is expected to hit 25m a year – a 70% increase."
Some of us might say that we live longer, so we have a higher chance to develop cancer. But the statistics are usually age adjusted, meaning that the number of newly diagnosed cancer cases increases within the same age group. It is also hard to ignore that Childhood Cancer is on the Rise.


Doctors and missionary doctors, from different parts of the world, consistently reported that cancer cases were very rare among populations living a traditional lifestyle.

We could argue that the reason behind the low number of diagnosed cancer cases, is the lack of technology of the time. However, this argument is not supported by the evidence that cancer cases were diagnosed in the settlers (usually European population), but not in the local population. This means that doctors were able to detect the disease. Somehow, the number of cancer cases in native populations - also increased following the adoption of a "western diet" (Diseases of Civilization).

Cancer Research

1. There is an increasing number of studies pointing to high glucose and insulin levels as risk factors for cancer. For instance, this study: Dietary glycemic load and colorectal cancer risk, concludes that:
"The positive associations of glycemic index and load with colorectal cancer suggest a detrimental role of refined carbohydrates in the etiology of the disease." (my emphasis)
Or, another study associating Metabolic Syndrome and cancer risk: Metabolic syndrome and the risk of breast cancer in postmenopausal women.
"This study supports a direct association between MetS [Metabolic Syndrome] and postmenopausal breast cancer risk."
Metabolic syndrome is characterized - among other disorders - by high insulin levels (as a result of high glucose levels), insulin resistance, and is also associated with weight-gain and diabetes.

2. Cancer is diagnosed with a PET-scan, based on research that cancer cells utilize glucose for fuel in order to multiply and spread.
"With a PET scan you have an injection of a very small amount of a radioactive drug (tracer) first. The amount of radiation is very small and no more than you have during a normal X-ray. It only stays in the body for a few hours. Depending on which drug you have, the radioactive drug will travel to particular parts of your body. The most common drug is fluorine 18, also known as FDG-18. This is a radioactive version of glucose.
When FDG-18 is injected into your body, it travels to places where glucose is used for energy. It shows up cancers because they use glucose in a different way from normal tissue. And it will show up changes in tissues that use glucose as their main source of energy - for example, the brain or heart muscle. Occasionally, it can show up areas of infection or inflammation."(my emphasis)
                                                          - (from Cancer Research UK)

Cancer as a Metabolic Disease

With the advancement of genetic research, a new hope has been unearthed regarding a possible cure for cancer. The problem with this research is that there are literally thousand and thousands of genetic variations between the nucleus of tumor cells. It seems impossible to analyze every single tumor for genetic variations and design a drug accordingly. It seems also impossible to test and to know the impact these drugs would have on healthy tissues.

According to the research of Thomas N. Seyfried (Boston College), researchers should shift their attention to considering cancer as a metabolic disease (energy production), rather than a genetic condition. In his study (Cancer as a metabolic disease: implications for novel therapeutics), Seyfried argues that the genetic damage occurring within the nucleus (DNA) of the cancer cells, are a result of malfunctioning mitochondria (the powerhouse of our cells, responsible for producing energy). A faulty genetic component in the nucleus does not necessarily cause damage to the mitochondria, but the opposite - a faulty mitochondria damaging the nuclear DNA - seems to be more plausible.
"Emerging evidence indicates that cancer is primarily a metabolic disease involving disturbances in energy production through respiration and fermentation. The genomic instability observed in tumor cells and all other recognized hallmarks of cancer are considered downstream epiphenomena of the initial disturbance of cellular energy metabolism."

This implies that therapeutic methods should be focusing on designing drugs which restore healthy mitochondria to these cells, or simply knock the damaged cells out, in order to prevent their proliferation.

Damaged mitochondria found in cancer cells cannot use oxygen efficiently, therefore these damaged cells switch to glycolysis (the use of glucose for energy) to survive and multiply.
"It is expected that an upregulation of glycolytic genes would be needed to facilitate compensatory energy production through glycolysis when cellular respiration is deficient for protracted periods." (my emphasis)

"No tumor cells have yet been described with a normal content and composition of cardiolipin [the building block of the waves inside the mitochondria]. Cells cannot respire effectively if the content or composition of their cardiolipin is abnormal."

Therefore, if we could inhibit, somehow, the metabolism of these cancer cells (glycolysis), then they would starve, and stop proliferating. For this, Seyfried experimented with a diet restricted in carbohydrates (high-fat diet). Carbohydrates are the source of glucose and the primary fuel for cancer cells. On a high fat diet, the body relies on ketone bodies for energy. In order to use ketone bodies, cells require healthy functioning mitochondria. Cancer cells lack this kind of mitochondria, therefore they are unable to utilize ketones as fuel. As a high fat diet is, by definition, low in glucose, it seems to be the ideal diet to starve cancer cells.
"A dependency on glucose and an inability to use ketones for energy makes tumor cells selectively vulnerable to this therapy."
"This therapeutic strategy produces a shift in metabolic physiology that will not only kill tumor cells but also enhance the general health and metabolic efficiency of normal cells, and consequently the whole body. We view this therapeutic approach as a type of ‘mitochondrial enhancement therapy’."

The role of Metformin (an anti-diabetic drug)

Metformin is used by diabetics to control blood sugar (glucose) levels. Researchers observed that people on Metformin, have a reduced risk of developing cancer:

Metformin and reduced risk of cancer in diabetic patients
Metformin Boosts Survival in Diabetic Cancer Patients.
Metformin for breast cancer less effective at higher glucose concentrations
These articles also seem to point to the relationship between high-glucose levels and the risk of cancer.

Cancer, an aggressive disease

In order to make things more complicated, there are certain types of cancer that are able to switch from glycolysis (utilization of glucose for energy) to the use of glutamine (an amino acid found in abundance in our body) for fuel, and this article talks about this switch: How cancer cells rewire their metabolism to survive.

We, and even our cells, are designed to survive under stress (when a preferred fuel is not available). Cancer cells seem to be no different. Cancer cells are able to change their fuel from glucose to other sources of energy, making researchers job more difficult in finding the right therapeutics to fight this disease.

However, as I was reading the actual study (Control of Nutrient Stress-Induced Metabolic Reprogramming by PKCz in Tumorigenesis) the article is based on, I discovered the initial cancer cells all start out as cells relying on glycolysis. This implies, that constant ,very low-glucose levels are required in order to prevent cells from proliferating.

Then, as I was reading the study, one sentence caught my eye:
"Another set of mutant mice was fed a Western diet (WD) to accelerate the appearance of tumors." (my emphasis)
This means, that in order to induce cancer in these mice, they had to feed them a Western diet, which we all know, is very high in sugar and refined carbohydrates, a very good source of glucose. This is equivalent to saying: Let's feed these animals some kind of poison and see what kind of drugs could be developed to knock out these different genes. Or: Let's poison them, and develop an antidote.

This study again seems to confirm that a Western diet is accelerating cancer growth and researchers know about it. Therefore, the best advice we could give cancer patients is to come off this Western diet, in order to extend their life expectancy. (It might be necessary to combine this dietary therapy with drugs that target those cancer cells, able to change their metabolism from glycolysis to other fuel sources).

I highly recommend this interview, to know more about the role of a ketogenic diet in cancer therapy.

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